The diagnostic potential of CD8 T cell subsets in the context of past viral exposures

Recent advances have been made in deciphering the T cell repertoire (TCR) in individuals previously exposed to viral pathogens in the context of laboratory diagnostics. However, no method yet offers information on the timing of the exposure. This limits the use of such technologies in diagnostic settings
where differentiation between acute/active infections and old/previous pathogen exposures is crucial. TCR sequencing focussing on the memory T cell subset that holds imprints of past pathogen exposures could close this technologic gap. Such information would particularly be impactful in the context of congenital
infectious disease (e.g., Zika virus and CMV), where primo infections (and re-activations of latent infections) are most relevant during the first trimester of pregnancy. Exclusion of recent exposure can be challenging with state-of-the-art diagnostics (serology). In this jPPP, we want to provide the first proof of concept that virus-specific T cells in the activated T cell subset divided by virus recognizing T cells in the memory T cell subset distinguishes recent from old viral exposures. We intend to provide full conceptual evidence for the SARS-CoV-2 use case (WP1) and initiate construction of a new diagnostic test for CMV (WP2 and 3), from which the follow-up trajectory will be built.